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Old 01-18-2013, 12:51 PM   #1
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How LDLC is calcuated.

I was perplexed by the so-called Friedewald equation for calculating the concentration of cholesterol carried by low-density lipoproteins (LDLC) in blood serum:

LDLC = total C - HDLC - triglycerides/5

Those of you with a background in biochemistry might wonder how "tryglycerides/5" becomes part of the equation. Triglycerides, other than being non-water-soluble (hydrophobic) would have nothing to do with cholesterol chemically. So why is the concentration of one being used to estimate the concentration of a sub-fraction of the other?

Think about it. It is like trying to estimate the number of black cats in your neighborhood by dividing the number of dogs by five. Right?

Okay, I actually dug up an old paper by Friedewald and some of his colleagues here. It is actually fairly simple.

First, there are a couple of chemical tests ("assays" as they are known in the biz) involved. One for cholesterol and one for triglycerides. You can perform them on blood serum to get a "total cholesterol" and "total triglycerides". Again, neither of these chemicals are miscible with water so your body usually packages them up in "vesicles" of a sort, called lipoproteins that hold all the hydrophobic molecules in a drop surrounded by a skin of molecules that are hydrophobic on one side and hydrophilic on the other.

At some point lipidologists must have decided that their job was too easy and they needed to classify these lipoproteins by their density. Like were they beachballs that would float to the top of a bottle of serum, sandbags that would sink to the bottom, or something in between.

Anyway, I think initially they just went the Goldilocks route and chose high, low and very low density lipoproteins (HDL, LDL and VLDL). There is an even lower density, giant one called a "chylomicron", but lets pretend like that one doesn't exist.

Then at some point they decided that somehow the cholesterol in the LDL was "bad" and the cholesterol in the HDL was "good", which led to a serious problem. That is, it was easy to sort the HDL lipoproteins from the others just using a normal centrifuge. But to separate the others required some serious hardware, an "ultracentrifuge". So it was much more expensive to do and more time consuming.

Then Friedewald seems to have come to a couple of conclusions:

(1) Pretty much all the blood triglycerides are in VLDLs and further more
(2) The concentration of triglycerides/cholesterol in VLDLs is 5:1 for the most part.

Ah hah! said Friedewald, I don't need to run my ultracentrifuge day and night any more to determine LDLC. I just determine total cholesterol and then subtract out the cholesterol that is in HDL and my estimate of the cholesterol in VLDL (which just happens to usually be the concentration of triglycerides divided by 5) and whatever remains must, ipso facto, be from LDL!!!

Thus the Friedewald equation was born.

At least that is my take.

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Old 01-18-2013, 01:09 PM   #2
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Thanks. That was a nice explanation.

I seem to remember that the Friedewald equation is not very accurate if the triglycerides are very low --- as they often are in LC'ers. Do you know anything about this?

Thanks.
Glenn in Omaha
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Old 01-18-2013, 03:05 PM   #3
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Great post Phillip!

I'll probably link to it in next months intro to our thread
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Old 01-19-2013, 07:02 AM   #4
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Quote:
Originally Posted by SabreCat50 View Post
Thanks. That was a nice explanation.

I seem to remember that the Friedewald equation is not very accurate if the triglycerides are very low --- as they often are in LC'ers. Do you know anything about this?

Thanks.
Glenn in Omaha
It fails for people with very high triglyceride concentrations quite a bit. (Friedewald et al. actually address this in the above linked-to paper.) Low triglycerides? Yeah, I don't know. I think it is pretty uncommon to have low trigs eating SAD, so that would be a very tiny pool of people. It would be not at all surprising if your body was producing much lower concentrations of triglycerides that it repackaged its lipids in a way that the Friedewald equation would not give an accurate answer.

Of course I think we would all prefer if the researchers could figure out what exactly is causing cardiovascular disease at a cellular/molecular level so all these attempt to alter the lipid compositions via diet and drugs could be targeted optimally or abandoned altogether.

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Old 01-19-2013, 07:03 AM   #5
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Originally Posted by reddarin View Post
Great post Phillip!

I'll probably link to it in next months intro to our thread
Thanks Red!

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Old 01-19-2013, 08:05 AM   #6
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Originally Posted by NKSL55 View Post
It fails for people with very high triglyceride concentrations quite a bit. (Friedewald et al. actually address this in the above linked-to paper.) Low triglycerides? Yeah, I don't know. I think it is pretty uncommon to have low trigs eating SAD, so that would be a very tiny pool of people. It would be not at all surprising if your body was producing much lower concentrations of triglycerides that it repackaged its lipids in a way that the Friedewald equation would not give an accurate answer.

Of course I think we would all prefer if the researchers could figure out what exactly is causing cardiovascular disease at a cellular/molecular level so all these attempt to alter the lipid compositions via diet and drugs could be targeted optimally or abandoned altogether.

--
Phillip
I googled and found the following article on PUB-MED.

Quote:
Arch Iran Med. 2008 May;11(3):318-21. doi: 08113/AIM.0014.
The impact of low serum triglyceride on LDL-cholesterol estimation.
Ahmadi SA, Boroumand MA, Gohari-Moghaddam K, Tajik P, Dibaj SM.
Source
Department of Pathology, Sina Hospital, Medical Sciences/ University of Tehran, Tehran, Iran.
Abstract
Most clinical laboratories directly measure serum triglyceride, total cholesterol, and high- density lipoprotein cholesterol. They indirectly calculate low-density lipoprotein cholesterol value using the Friedewald equation. Although high serum triglyceride (>400 mg/dL or 4.52 mmol/L) devaluates low-density lipoprotein cholesterol calculation by using this formula, effects of low serum triglyceride (<100 mg/dL or 1.13 mmol/L) on its accuracy is less defined.Two hundred thirty serum samples were assayed during a one-year period. In 115 samples, the triglyceride level was below 100 mg/dL and in 115 samples from age- and sex-matched patients the triglyceride level was 150 - 350 mg/dL (1.69 - 3.95 mmol/L). In both groups total cholesterol was above 250 mg/dL (6.46 mmol/L). On each sample, total cholesterol, high-density lipoprotein cholesterol, and triglyceride were directly measured in duplicate and low-density lipoprotein cholesterol measured directly and calculated with Friedewald equation as well. Statistical analysis showed that when triglyceride is <100 mg/dL, calculated low- density lipoprotein cholesterol is significantly overestimated (average :12.17 mg/dL or 0.31 mmol/L), where as when triglyceride is between 150 and 300 mg/dL no significant difference between calculated and measured low-density lipoprotein cholesterol is observed. In patients with low serum triglyceride and undesirably high total cholesterol levels, Friedewald equation may overestimate low-density lipoprotein cholesterol concentration and it should be either directly assayed or be calculated by a modified Friedewald equation. Using linear regression modeling, we propose a modified equation.
PMID: 18426324 [PubMed - indexed for MEDLINE] Free full text
So, low triglycerides (<100) cause LDL calculations to be OVERestimated. Here is a link that calculates the LDL using both the Friedewald and "Iranian" formulas.

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Old 01-19-2013, 08:44 AM   #7
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Quote:
Originally Posted by NKSL55 View Post
It fails for people with very high triglyceride concentrations quite a bit. (Friedewald et al. actually address this in the above linked-to paper.) Low triglycerides? Yeah, I don't know. I think it is pretty uncommon to have low trigs eating SAD, so that would be a very tiny pool of people. It would be not at all surprising if your body was producing much lower concentrations of triglycerides that it repackaged its lipids in a way that the Friedewald equation would not give an accurate answer.

Of course I think we would all prefer if the researchers could figure out what exactly is causing cardiovascular disease at a cellular/molecular level so all these attempt to alter the lipid compositions via diet and drugs could be targeted optimally or abandoned altogether.

--
Phillip
Google: The Blog of Michael R. Eades, M.D.Low-carbohydrate diets increase LDL: debunking the myth » The Blog of Michael R. Eades, M.D.

There is quite a bit of info on low trig levels in LCers and how that messes with the Friedewald equation.

Last edited by drjlocarb; 01-19-2013 at 09:33 AM..
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Old 01-19-2013, 09:18 AM   #8
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Originally Posted by drjlocarb View Post
Google: The Blog of Michael R. Eades, M.D.Low-carbohydrate diets increase LDL: debunking the myth » The Blog of Michael R. Eades, M.D.

There is quite a bit of info on low trig levels in LCers and how that messes the Friedewald equation.
I had forgotten about Eades' excellent blog article. I just reread it and he also cites the Iranian paper I mentioned above.

Has anyone here had the VAP test? Through your doctor or on your own?

Thanks,
Glenn in Omaha
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